An ischemic injury refers to a tissue injury caused by restriction in blood supply to organs requiring blood supply such as the heart, brain, kidneys, etc. (myocardial infarction, cerebral infarction, renal infarction, etc.), leading to dysfunction of the organs and increased mortality rate. The ischemic injury causes fatal complications of the heart, brain, kidneys, etc., increases the risk of acute rejection in organ transplantation and, in the long term, decreases the survival rate of the transplanted organ.
Substantial shortage of oxygen supply due to ischemia induces a pathological condition known as hypoxia. Prolonged ischemia and hypoxia can lead to functional loss of tissue and even cell death. Various spontaneous and iatrogenic pathological conditions induce ischemia and hypoxia. Non-limiting examples include vascular obstructive disease, coronary thrombosis, cerebrovascular thrombosis, aneurysm rupture, systemic hemorrhage, crush injury, sepsis, severe skin burn, vascular ligation surgery (e.g., spinal ischemia following thoracoabdominal aneurysm surgery), cardiopulmonary bypass, organ transplantation, cardiopulmonary collapse (sudden cardiac death), suffocation, etc.
In general, ischemia and hypoxia caused thereby are treated by restoring blood and oxygen supply to a normal level by increasing systemic oxygen supply or removing the cause of vascular occlusion. When compared with the situation where ischemia or hypoxia is prolonged, it is expected an improved result may be obtained by restoring blood supply. However, during the restoration of blood and oxygen supply, cell death or functional loss may be additionally induced apart from the damage caused by ischemia or hypoxia.
The additional damage induced during the restoration of blood and oxygen supply is known as reperfusion injury. The paradoxical tissue injury caused by reperfusion injury appears to be similar to an acute inflammatory condition resulting from the adherence of inflammatory cells to the reperfused tissues, activation of the inflammatory cells and subsequent generation of free radicals [Granger et al. Ann. Rev. Physiol., 57, 311-332, (1995)]. The generation of free radicals and other cytotoxic biomolecules within the reperfused tissue can induce cell death by activation of necrotic or apoptotic pathway.
Ischemic-reperfusion (IR) tissue injury occurring during organ transplantation results in deferred restoration of organ function after the organ transplantation and this often is an undesired prognostic sign in the maintenance of the function of the transplanted organ in the long term due to inflammatory tissue response. The initial ischemic-reperfusion injury occurring incidentally with the transplantation of organs, particularly kidneys, can lead to subsequent organ failure and transplant rejection.
Recently, renal ischemic-reperfusion injury (IRI) has been newly identified as one of acute inflammatory responses in which the inflammatory cells of both the innate immune system and the acquired immune system are involved.
A flap refers to a skin or tissue which is lifted from a site of the body and moved to another site, which includes a blood vessel that allows survival of the tissue. Flap surgery is used for lost soft tissue, chronic wound, etc. that cannot be treated with, for example, skin grafting. It is a surgical method the most frequently used in plastic and reconstructive surgery. In particular, it is advantageous in that primary reconstruction is possible through transplantation of various complex tissues including bone, tendon, muscle, nerve, etc., thereby allowing fast restoration. In the flap surgery, the survival rate of the flap is very important in the treatment of ischemic-reperfusion injury. Accordingly, a method of stably improving the flap survival rate will be very useful.
As described, an effective method for treating the frequently occurring ischemic-reperfusion injury is not readily available. Therefore, an effective method for preventing and treating ischemic-reperfusion injury will be valuable.